Biochemistry Research Group, Biological Sciences, University of Calgary, Calgary, Alberta, Canada.
J Toxicol Environ Health A. 2011;74(22-24):1476-92. doi: 10.1080/15287394.2011.618977.
Chronic wasting disease (CWD) is a fatal neurodegenerative disease affecting both farmed and wild cervids, specifically deer and elk, and is a member of the larger family of prion diseases. Prion disease transmission is believed to occur through exposure to infectious prion material-a misfolded and infectious form of the prion protein that is normally present in the host. Chronic wasting disease is endemic to regions of central North America and infectious material can persist for long periods in the environment, posing challenges for remediation and monitoring. The current methods of detection are relatively invasive, require the host animal to be in intermediate to late stages of disease incubation, and are not without risk to those collecting samples. The potential for a blood test that could identify key biomarkers of disease incubation is of great interest. Serum from elk (Cervus elaphus) (n = 4) was collected on a monthly schedule before, and following, oral inoculation of CWD-positive homogenate, and collection continued until clinical signs were apparent. Blood was collected on the same schedule for a group of control animals (n = 2) housed under identical conditions. Targeted profiling, using (1)H-nuclear magnetic resonance (NMR) spectroscopy, of serum metabolites was used to yield metabolite identification as well as quantitation. Hierarchical multivariate statistical orthogonal partial least-squares (O-PLS) models were generated to identify predictive components in the data. Due to the duration of the study (25 mo) a significant aging component was taken into account during analysis. Several metabolites were correlated with aging in elk inoculated with CWD, but not in the control group.
慢性消瘦病(CWD)是一种影响养殖和野生鹿科动物(特别是鹿和麋鹿)的致命神经退行性疾病,是朊病毒病大家族的成员。据信,朊病毒疾病的传播是通过接触传染性朊病毒物质(一种错误折叠和传染性形式的朊病毒蛋白,通常存在于宿主中)发生的。慢性消瘦病在北美中部地区流行,传染性物质在环境中可以长时间存在,这给修复和监测带来了挑战。目前的检测方法相对具有侵入性,需要宿主动物处于疾病潜伏期的中晚期,并且采集样本的人也存在一定风险。能够识别疾病潜伏期关键生物标志物的血液检测方法具有很大的吸引力。每月采集 elk(Cervus elaphus)血清(n = 4),在口服接种 CWD 阳性匀浆之前和之后进行,并继续采集,直到出现临床症状。在相同条件下饲养的一组对照动物(n = 2)也按照相同的时间表采集血液。使用(1)H 核磁共振(NMR)光谱对血清代谢物进行靶向分析,以获得代谢物的鉴定和定量。生成分层多变量正交偏最小二乘(O-PLS)模型,以识别数据中的预测成分。由于研究时间长(25 个月),在分析过程中考虑了显著的老化因素。在接种 CWD 的 elk 中,有几个代谢物与衰老相关,但在对照组中没有。